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Skin whitening is the practice of using substances, mixtures, or physical treatments to lighten skin color. Skin whitening treatments work by reducing the content of melanin of the skin. Many agents have been shown to be effective in skin whitening.
Specific zones of abnormally high pigmentation such as lentigo spots, moles and birthmarks may be de-pigmented to match to the surrounding skin. In cases of vitiligo, unaffected skin may be lightened to achieve a more uniform appearance.
Discovery and design
Melanogenesis inhibitors have been discovered and developed through several methods, including: screening of synthetic chemical libraries (high-throughput screening is occasionally used), screening of plant extracts, computational (in silico) search, found as a side effect of previously known drugs and exploration of structural analogues of previously known tyrosinase inhibitors based on knowledge (in varying degrees) of their structure-activity relationship. Thus, the development and discovery of melanogenesis inhibitors illustrates many of the methods used in drug design. Some of the most potent competitive reversible tyrosinase inhibitors are synthetic compounds with a potency hundreds of times that of kojic acid.
Mechanisms of action
Melanin is the main substance responsible for the color of the skin. Melanin is class of dark polymers generated by the body through the process of melanogenesis. Among the melanin pigmenting the skin and hair, 2 types can be distinguished based on its chemical composition and biological route of synthesis: the black/brown eumelanin and the red/yellow pheomelanin. The variation of skin color among individuals is mostly because of variation of the content of melanin in the skin. Skin with little or no melanin is almost white. Other factors influence skin color in a lesser degree, including the amount of blood in blood vessels (because of the color of blood), skin thickness and content of carotenoids in skin.
Melanin in synthesized in melanosomes which are organelles produced in melanocytes. Melanocytes are cells dedicated to this function that are present in the skin, hair follicles, and other structures of the body. The synthesis of melanin (also called" melanogenesis" and" melanization") involves a chain of enzyme-catalyzed chemical reactions and non-enzyme-catalyzed reactions. The main precursor to melanin is l-tyrosine. The first step of melanogenesis is the conversion of l-tyrosine to l-dopa; this is the first and rate-limiting step and is catalized by the enzyme tyrosinase. Other enzymes involved in the synthesis include tyrosinase-related protein 1 (trp1) and tyrosinase-related protein 2 (trp2); trp2 is also known as" dopachorome tautomerase" (dct). L-tyrosine is taken by the melanocytes from the intercellular medium, then transported to the melanosomes. L-tyrosine is also synthesized within the melanocytes from l-phenylalanine by the enzyme phenylalanine-hydroxylas (pah)
Melanosomes are transferred to keratinocytes (the most abundant cell type in the skin). Most of the melanin of skin is found in keratinocytes. Additionally, melanocytes interact with keratinocytes through chemical signaling.